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Creative Data Solutions (CDS) is a Vanderbilt Shared Resource and has extensive experience in providing effective and robust solutions to challenges pertaining to research data using modern informatics and bioinformatics approaches.

Description: James M. May's research has
been in the area of diabetes for the last 35 years, initially on
mechanisms of glucose transport, and for the last 15 years on
antioxidant function in atherosclerosis and diabetes. His
laboratory uses murine models of type 1 diabetes to understand the
damage of oxidative stress related to high glucoses (glucotoxicity)
to the endothelial cells that line all blood vessels. Vitamin C is
being studied as a potential therapeutic intervention. This Vitamin
is beneficial to the endothelium because it scavenges reactive
oxygen and nitrogen molecules that would otherwise damage the
cells. Perhaps more important, Vitamin C is required as a co-factor
by several enzymes that function to hydroxylate collagen,
cholesterol, carnitine, the transcription factor HIF-1α, and many
neurotransmitters. Recent results from this laboratory have shown
that it tightens the endothelial barrier to the transit of large
molecules such as albumin from the blood vessel to the interstitial
space. By doing this, Vitamin C could decrease tissue edema that is
a problem with high glucoses. The effect of Vitamin C to improve
endothelial barrier function was first shown in cultured human
umbilical vein endothelial cells, but now has been extended to
primary culture cells from human dermis and the blood-brain
barrier. The mechanism of the effect has not been fully elucidated,
but appears in part to relate to the ability of Vitamin C to spare
tetrahydrobiopterin, a crucial co-factor for endothelial nitric
oxide synthase. In so doing, Vitamin C increases the generation of
nitric oxide, which can both help to dilate vessels, but also to
tighten the endothelial barrier. Studies in mice also suggest that
Vitamin C can decrease trans-endothelial leakage caused by both
Vitamin C deficiency and by high glucoses due to diabetes.
Activation of the receptor for advanced glycation end products
(RAGE) by high glucose is one of the major damaging actions of
glucose, and Vitamin C prevents increases in endothelial
permeability due to RAGE agonists. Studies are now focused on novel
mouse models of Vitamin C deficiency and excess to test effects of
diabetes and to determine whether Vitamin C excess or repletion can
decrease systemic damage to the endothelium by high glucose.